The present invention relates to methods and compositions useful for the detection of Acquired Immune Deficiency Syndrome (AIDS). More particularly, this invention relates to antibodies which react positively with human AIDS tissues.
Acquired Immune Deficiency Syndrome (AIDS), also known as Gay-Related Immune Deficiency or Gay Compromise Syndrome is apparently a new disease of man which prior to 1981 was not recognized as a specific disease entity. To date, with over 4,000 cases reported, the disease has elicited great concern because the epidemic is quickly expanding and the disease exhibits a very high mortality rate.
At present, the disease is defined by its clinical features, as no specific diagnostic test has been reported. Young infants (less than 28 days) and the elderly (over 60 years) are excluded by definition, as other causes of deficient cellular immunity can affect these age groups. Also by definition, all other known causes of immune deficiency such as a neoplasm (except those specifically associated with AIDS), immunosuppressive therapy, corticosteroid therapy and renal failure are excluded. To be diagnosed as having AIDS, a patient must have a disease that specifically indicates a deficiency in cellular immunity such as Kaposi's sarcoma, primary central nervous system lymphoma, progressive multi-focal leukoencephalopathy, or infections with a variety of organisms that are not usually seen as pathogens, including Pneumocystis carinii, Toxoplasma gondii, cryptosporidium, cytomegalovirus, disseminated fungal infections particularly with Aspergillus, Cryptococcus, Candida, Nocardia, disseminated herpes viruses, atypical Mycobacteria, or uncontrolled Strongyloides stercoralis infestation. Typically more than one of these is seen in the patient and there are concomitant abnormalities of immune function which can be demonstrated by laboratory tests but which are not specific to AIDS. Kaposi's sarcoma and Pneumocystis carinii pneumonia have been the most characteristic diseases. Once the characteristic clinical picture of AIDS is established in a patient, immune function does not revert to normal.
Prior to the development of AIDS, patients have a prodromal illness characterized by fever, weight loss and enlarged lymph nodes. This may last for weeks to years. This lymphadenopathy syndrome is not specific to AIDS, similar cases having been described long before AIDS appeared; and only a minority of patients with this clinical syndrome, even in high-risk groups, have gone on to develop AIDS.
The epidemiology of AIDS strongly suggests involvement of an infectious agent such as a virus. AIDS has been largely confined to homosexual and bisexual sexually promiscuous males, Haitians, intravenous drug abusers, hemophiliacs, and other recipients of blood and blood products. The disease has a very long incubation period, making the chains of transmission difficult to follow. The disease is transmitted with some difficulty and requiring either intimate contact, particularly anal intercourse, or actual transfer by blood.
A variety of agents have been suggested as possible causes. Viruses are regularly recovered from patients with the disease, including cytomegalovirus, Epstein-Barr virus, and adenoviruses. The most likely etiologic agents include retroviruses which have been cultured from a significant percentage of patients by investigators at the National Cancer Institute (NCI) and at the Institute Pasteur. The agent cultured at the NCI is characterized as a variant of the human T-cell leukemia virus, names HTLV-III. It has been cultured from a high percentage of patients with the prodromal syndrome. Although antibodies to it are seen in a high percentage of patients with AIDS, it has only been cultured from about one third of patients who actually have AIDS. Comparable data is presently available concerning the viruses cultured by the French workers. At this time, no proof exists that either of these viruses is in fact the cause of AIDS, although both groups claim that their virus is the cause.
Presently, there are no laboratory tests available which are specific for AIDS. A number of different abnormalities of immune function can be demonstrated, such as failure to respond to skin testing for common cellularimmunity-based recall antigens, altered blood lymphocyte levels, and altered ratios of helper and suppressor subsets of T-lymphocytes. These abnormalities are merely expressions of the immune defect and can be produced by many different causes. Abnormal levels of alpha-thymosin, alpha-interferon, neopterin and beta.sub.2 -microglobulin, have also been noticed. Again, these are nonspecific indicators and may reflect an immune defect or the presence of an inflammatory stimulus rather than any specific disease.
A specific test for AIDS requires an antibody or immunoprotein specific for the etiologic agent or something the etiologic agent produces in the involved tissues. The only candidate for such an antibody has been derived from patients with AIDS or the pre-AIDS syndrome. These antibodies which can be used to identify viral components in AIDS tissue require a difficult and tedious assay procedure. Although antibodies directed against HLTV-III are presently being developed, they may still require difficult assay procedure to elicit detection of AIDS. Moreover, there is no conclusive proof that HTLV-III is the cause of AIDS.
Several animal models have been suggested as closely related to AIDS, including AIDS-like diseases in rhesus monkeys and macaques. Viruses have been cultured from these animals, but these viruses do not appear to be related to HTLV-III. These animals do not survive the disease and have not been reported as a source of antibodies. Attempts have also been made to transfer the human disease to rhesus monkeys and chimpanzees, but neither viruses nor antibodies have been reported from these animals. At present there is no recognized animal model for AIDS.
Accordingly, there is a great need for a diagnostic test or procedure capable of detecting AIDS in a suspected carrier.